External Beam Breast and Chest Wall Re-Irradiation Following Resection of Ipsilateral Breast Cancer Recurrence: Dose-Toxicity Relationships and Long-Term Oncologic Outcomes.

Background/Objectives: Breast/chest wall (B/CW) re-irradiation (reRT) is approached cautiously because of concerns regarding late toxicity and uncertain benefit. Contemporary data on mature toxicity and oncologic outcomes after external beam photon reRT are limited. Methods: This retrospective cohort included 113 consecutive patients who completed reRT after resection of locoregionally recurrent breast cancer between 2010 and 2024. The primary endpoint was cumulative incidence of late grade ≥ 2 CTCAE toxicity, analyzed using competing-risks methods. Secondary endpoints were locoregional recurrence-free survival (LRRFS) and local failure (LF), assessed using Kaplan-Meier, Cox regression, and Fine-Gray modeling. Results: Median age at reRT was 66 years. Most recurrences were early-stage (72.6%) and hormone receptor-positive (68.1%). Median cumulative EQD2 was 94.9 Gy, and 25.7% received IMRT. At 67.1 months' median follow-up, 5-year cumulative incidences of grade ≥ 2 and grade 3 toxicity were 35.4% (95% CI, 25.6-45.1) and 3.9% (95% CI, 0.1-7.8), respectively. Higher cumulative EQD2 predicted grade ≥ 2 toxicity (SHR, 1.94 per 10 Gy; p < 0.001) and grade 3 toxicity (SHR, 4.32 per 10 Gy; p < 0.001). Longer interval between radiotherapy courses (p = 0.029) and IMRT (SHR, 0.40; p = 0.005) were associated with lower grade ≥ 2 toxicity. Five-year LRRFS was 84.2% (95% CI, 76.7-92.4), and LF was 6.8%. Advanced-stage disease and second or subsequent recurrence predicted inferior LRRFS. Partial B/CW reRT did not compromise disease control in early-stage recurrences. Conclusions: Adjuvant breast and chest wall re-irradiation using external photons achieved durable locoregional control with low rates of severe late toxicity in one of the largest reported cohorts. These findings support individualized curative-intent reRT guided by cumulative dose, technique, and recurrence risk.